Inositol monophosphatase, SuhB (IPR022337)

Family relationships

Description

Inositol polyphosphate 1-phosphatase (1PTASE) and inositol monophosphatase (MPTASE) are enzymes of the inositol signalling pathway that share similar enzymatic activity [PMID: 7761465]. Both enzymes exhibit an absolute requirement for metal ions (Mg2+ is preferred), and both are uncompetitively inhibited by submillimolar concentrations of Li+. Their amino acid sequences contain a number of conserved motifs, which are also shared by several other proteins related to MPTASE (including products of fungal QaX and qutG, bacterial suhB and cysQ, and yeast hal2) [PMID: 7761465].

Structural analysis of these proteins has revealed a common core of 155 residues: the core comprises 5 alpha-helices and 11 beta-strands, and includes residues essential for metal binding and catalysis. While the core has been conserved, presumably to impart catalytic function, the loops and regions of structure outside the core have evolved unique regulatory domains [PMID: 7761465].

An interesting property of the enzymes of this family is their sensitivity to Li+ at levels achieved in patients undergoing therapy for manic depression. The targets and mechanism of action of Li+ are unknown, but over-active inositol phosphate signalling may account for symptoms of the disease [PMID: 2553271, PMID: 15858264]. It has been proposed that these Li+-sensitive proteins could represent targets for Li+ in manic depressive disease [PMID: 7761465, PMID: 15858264, PMID: 10822345].

The structures of several members of the superfamily have been determined by X-ray crystallography [PMID: 15858264, PMID: 8068621]. The fold of fructose 1,6-bisphosphatase (FBPTASE) was noted to be identical to that of MPTASE [PMID: 10747806]. The suhB gene product from Escherichia coli, which is thought to participate in post-transcriptional control of gene expression, also possesses inositol-1-phosphatase activity [PMID: 10747806, PMID: 8002619]. The major difference between this enzyme from other characterised inositol-1-phosphatases is that it exists as a monomer in solution (rather than a dimer or tetramer); it is also more hydrophobic - it is thought that these physical differences might underlie the biological role of wild-type SuhB in E.coli [PMID: 10747806].